NM_003002.4(SDHD):c.361C>T (p.Gln121Ter) AND multiple conditions

Clinical significance:Pathogenic (Last evaluated: Sep 9, 2020)

Review status:1 star out of maximum of 4 stars

criteria provided, single submitter

Based on:
1 submission [Details]
Record status:
current
Accession:
RCV000226232.4

Allele description [Variation Report for NM_003002.4(SDHD):c.361C>T (p.Gln121Ter)]

NM_003002.4(SDHD):c.361C>T (p.Gln121Ter)

Gene:
SDHD:succinate dehydrogenase complex subunit D [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
11q23.1
Genomic location:
Preferred name:
NM_003002.4(SDHD):c.361C>T (p.Gln121Ter)
HGVS:
  • NC_000011.10:g.112094851C>T
  • NG_012337.3:g.13005C>T
  • NM_001276503.2:c.216C>T
  • NM_001276504.2:c.244C>T
  • NM_001276506.2:c.*59C>T
  • NM_003002.4:c.361C>TMANE SELECT
  • NP_001263432.1:p.Cys72=
  • NP_001263433.1:p.Gln82Ter
  • NP_002993.1:p.Gln121Ter
  • LRG_9t1:c.361C>T
  • LRG_9:g.13005C>T
  • LRG_9p1:p.Gln121Ter
  • NC_000011.9:g.111965575C>T
  • NM_003002.3:c.361C>T
  • NR_077060.2:n.450C>T
Protein change:
Q121*
Links:
dbSNP: rs878854594
NCBI 1000 Genomes Browser:
rs878854594
Molecular consequence:
  • NM_001276506.2:c.*59C>T - 3 prime UTR variant - [Sequence Ontology: SO:0001624]
  • NR_077060.2:n.450C>T - non-coding transcript variant - [Sequence Ontology: SO:0001619]
  • NM_001276504.2:c.244C>T - nonsense - [Sequence Ontology: SO:0001587]
  • NM_003002.4:c.361C>T - nonsense - [Sequence Ontology: SO:0001587]
  • NM_001276503.2:c.216C>T - synonymous variant - [Sequence Ontology: SO:0001819]

Condition(s)

Name:
Carney-Stratakis syndrome
Synonyms:
Paraganglioma and gastric stromal sarcoma; Paraganglioma and gastrointestinal stromal tumor; Paraganglioma and GIST; See all synonyms [MedGen]
Identifiers:
MONDO: MONDO:0011740; MedGen: C1847319; Orphanet: 97286; OMIM: 606864
Name:
Pheochromocytoma
Synonyms:
Chromaffinoma; Chromaffin paraganglioma; Chromaffin tumor; See all synonyms [MedGen]
Identifiers:
MONDO: MONDO:0008233; MedGen: C0031511; Orphanet: 29072; OMIM: 171300; Human Phenotype Ontology: HP:0002666
Name:
Paragangliomas 1 (PGL1)
Synonyms:
PARAGANGLIOMA, CAROTID BODY; PARAGANGLIOMAS, FAMILIAL NONCHROMAFFIN, 1; PGL 1; See all synonyms [MedGen]
Identifiers:
MedGen: C1868633; Orphanet: 29072; OMIM: 168000
Name:
Cowden syndrome 3 (CWS3)
Identifiers:
MONDO: MONDO:0014045; MedGen: CN166604; Orphanet: 201

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Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV000287826Invitaecriteria provided, single submitter
Pathogenic
(Sep 9, 2020)
germlineclinical testing

PubMed (4)
[See all records that cite these PMIDs]

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineunknownnot providednot providednot providednot providednot providedclinical testing

Citations

PubMed

Germ-line mutations in nonsyndromic pheochromocytoma.

Neumann HP, Bausch B, McWhinney SR, Bender BU, Gimm O, Franke G, Schipper J, Klisch J, Altehoefer C, Zerres K, Januszewicz A, Eng C, Smith WM, Munk R, Manz T, Glaesker S, Apel TW, Treier M, Reineke M, Walz MK, Hoang-Vu C, Brauckhoff M, et al.

N Engl J Med. 2002 May 9;346(19):1459-66.

PubMed [citation]
PMID:
12000816

High prevalence of founder mutations of the succinate dehydrogenase genes in the Netherlands.

Hensen EF, van Duinen N, Jansen JC, Corssmit EP, Tops CM, Romijn JA, Vriends AH, van der Mey AG, Cornelisse CJ, Devilee P, Bayley JP.

Clin Genet. 2012 Mar;81(3):284-8. doi: 10.1111/j.1399-0004.2011.01653.x. Epub 2011 Mar 15.

PubMed [citation]
PMID:
21348866
See all PubMed Citations (4)

Details of each submission

From Invitae, SCV000287826.4

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (4)

Description

This sequence change results in a premature translational stop signal in the SDHD gene (p.Gln121*). While this is not anticipated to result in nonsense mediated decay, it is expected to delete the last 39 amino acids of the SDHD protein. This variant is not present in population databases (ExAC no frequency). This variant has been reported in an individual affected with pheochromocytoma (PMID: 12000816). While functional studies have not been performed to test the effects of this particular variant, a missense substitution (p.Leu139Pro) and a different truncation downstream of this variant (p.Ser132Glnfs*3), have been determined to be pathogenic (PMID: 21348866, 11391798, Invitae database). This suggests that deletion of these amino acid residues likely will disrupt SDHD function. For these reasons, this variant has been classified as Pathogenic.

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknownnot providednot providednot providednot providednot providednot providednot provided

Last Updated: Oct 7, 2021

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